Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig

• Published in: European journal of pharmacology 1999-11, Vol.383 (3), p.297-303
• Main Authors: Doi, Takayuki, Kamo, Izumi, Imai, Shigemitsu, Okanishi, Satoshi, Ishimaru, Takenori, Ikeura, Yoshinori, Natsugari, Hideaki
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dimethyl Sulfoxide - pharmacology; Guinea Pigs; lower; Male; Medical sciences; Micturition reflex; Naphthyridines - pharmacology; Non-peptide tachykinin NK 1 receptor antagonist; Pharmacology. Drug treatments; Piperidines - pharmacology; Pressure; Receptors, Tachykinin - antagonists & inhibitors; Reflex - drug effects; Reflex - physiology; Stereoisomerism; TAK-637; Urethra - drug effects; Urethra - physiology; Urinary Bladder - drug effects; Urinary Bladder - physiology; Urinary system; Urinary tract; Urination - drug effects; Urination - physiology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00657-3

The effects of TAK-637 (( aR,9 R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7 H-[1,4]diazocino[2,1- g][1,7]naphthyridine-6,13-dione), a novel tachykinin NK 1 receptor antagonist, on the micturition reflex in guinea pigs were studied in comparison with those of anti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0.03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethane-anesthetized guinea pigs, but they decreased voiding pressure, although the effect of propiverine was not statistically significant. A structurally unique tachykinin NK 1 receptor antagonist, (±)-CP-99,994 ((±)-(2 S,3 S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a minimum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the volume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties.